Intracranial sinus thrombosis in patient with Crohn disease and factor V Leiden mutation

Archives of Pathology & Laboratory Medicine,  Aug 2003  by Maag, Jennifer,  Prayson, Richard A

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* There is a well-known risk of thrombosis in patients with inflammatory bowel disease. Documented cases of intracranial sinus thrombosis in this setting are rare. We present the case of a 30-year-old man with Crohn disease who spontaneously developed a superior sagittal sinus thrombosis and bifrontal infarcts that resulted in death. The patient was heterozygous for factor V Leiden mutation. The literature was searched to assess the frequency of cerebral venous infarcts in inflammatory bowel disease and the role that factor V Leiden plays in thrombosis in such patients.

It is well recognized that patients with inflammatory bowel disease (IBD) have an increased risk of thrombosis compared to the rest of the population. In a larger series of 7199 patients with IBD, 1.3% (n = 92) suffered a thrombotic complication, excluding those complications that were related to atherosclerosis, diabetes, or obesity.1 Of the 92 patients affected, 9 had cerebral vessel involvement, none of which involved the sagittal sinus.1 Deep venous thrombosis and pulmonary emboli are the most common thrombotic complications in IBD.1-3 Markowitz et al2 reviewed a series of 36 cases of cerebral and retinal thromboembolic events in IBD patients in the literature and noted involvement of the venous circulation in 14 patients. Of these 14 patients, 6 died as a result of venous thrombosis. Ten suffered from ulcerative colitis, and 4 suffered from Crohn disease. The age range of these patients was 14 to 56 years (mean, 31 years). The presence or absence of any hypercoagulable states among the reported cases was not mentioned.2 Patients with IBD tend to suffer thrombosis earlier in life than thrombotic patients without IBD,3,4 with 75% of the events occurring in patients younger than 45 years.4 The mortality of thromboembolic events in the setting of IBD is significant-in the range of 8% to 25%.1,3

We report a fatal outcome in a young man with Crohn disease who developed severe venous thrombosis.

REPORT OF A CASE

A 30-year-old white man presented to the emergency department complaining of a 1-day history of headache and bilateral lower extremity weakness. His medical history was significant for Crohn disease, which, until recently, had been asymptomatic for some time. He was on no medications. While on a recent trip, he began to have bloody diarrhea and abdominal cramping. The day after his return home, his headache began. During his emergency department visit, he experienced mental status changes and rapidly became obtunded. A computed tomographic scan of the head demonstrated a superior sagittal sinus thrombosis and bilateral hemorrhagic infarcts of the parietal lobes (Figures 1 and 2). He underwent a procedure to recanalize the sagittal sinus using an AngioJet (Possis Medical, Minneapolis, Minn). However, an intraoperative magnetic resonance angiogram showed extensive external cerebral venous system thrombosis. The patient died shortly thereafter, less than 24 hours after presentation.

PATHOLOGIC FINDINGS

At autopsy, the superior sagittal sinus as well as the bilateral sigmoid and transverse sinuses were filled with acute thrombi that were adherent to the sinus walls (Figure 1, b). Bilateral frontoparietal hemorrhagic infarcts were present (Figure 2, b). The brain was diffusely edematous (weight, 1.56 kg), and bilateral cerebellar tonsillar herniation was evident. Thrombi were found in the microvascularure of the liver along with passive venous congestion. The colon was diffusely thickened, granular, and hemorrhagic. Microscopic sections demonstrated a dense lymphocytic infiltrate in the mucosa as well as thrombi in several of the submucosal vessels. The mucosa had undergone autolysis, making the architecture difficult to evaluate. The small bowel and remainder of the gastrointestinal tract were uninvolved.

Laboratory evaluations on premortem blood samples revealed the following: hemoglobin level, 12.8 g/dL (normal, 13.5-17.5 g/dL); platelet count, 61 x 10^sup 3^/[mu]L (normal, 150-400 x 10^sup 3^/[mu]L); activated partial thromboplastin time, 29.1 seconds (normal, 21.5-32.5 seconds); prothrombin time, 19.3 seconds (normal, 8.0-13.3 seconds); international normalized ratio, 1.69 (normal, 0.81-1.21); D-dimer, >20 000 ng/mL (normal, 250 ng/mL); fibrinogen, 0.177 g/dL (normal, 0.2-0.4 g/dL) (5.21 [mu]mol/L [normal, 5.88-11.76 [mu]mol/L]); antithrombin III, 79 mg/dL (normal, 23-32 mg/dL); protein S, 31% of normal (59%-140% of normal); protein C, 38% of normal (70%-120% of normal); and plasminogen, 50% of normal (68%-122% of normal). These findings were interpreted as being consistent with disseminated intravascular coagulation. Polymerase chain reaction gene studies were negative for methylenetetrahydrafolate reductase polymorphism and for the prothrombin G20210A mutation. The patient was heterozygous for factor V Leiden mutation, with the replacement of arginine by glutamine at position 506.

Colonic biopsies performed 5 years previously demonstrated focal architectural distortion of the crypts, thickened muscularis propria, and basal plasmacytosis. No granulomas were identified, and there was no evidence of dysplasia. The focal distribution of these findings, evidenced by skip lesions and sparing of the rectum, was interpreted as being consistent with Crohn disease.